A Smart Nano-Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy

作者：Meng, Hao; Zou, Yan; Zhong, Ping; Meng, Fenghua^*; Zhang, Jian; Cheng, Ru; Zhong, Zhiyuan^*

来源：Macromolecular Bioscience, 2017, 17(10): 1600518.

DOI：10.1002/mabi.201600518

• active targeting
• melanoma
• polymer-drug conjugate
• polymersomes
• reduction-sensitive

Nano-prodrugs usually involve a multistep synthesis which largely compromises their benefits. Here, a smart nano-prodrug platform with reactive drug loading, superb stability, and triggered drug release is reported for targeted melanoma therapy. cRGD-decorated polymersomal mertansine prodrug (cRGD-PS-DM1) is readily fabricated from cRGD-functionalized poly(ethylene glycol)-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) with simultaneous loading of mertansine (DM1) via thiol-disulfide exchange reaction and disulfide cross-linking of polymersomal membrane. cRGD-PS-DM1 exhibits a size of approximate to 100 nm, little drug leakage, and fast DM1 release in the presence of 2 x 10(-3)-10 x 10(-3) m glutathione. Tetrazolium-based colorimetric assay (MTT) and confocal microscopy studies confirm effective homing of cRGD-PS-DM1 to (v3) overexpressing B16F10 melanoma cells. Notably, the in vivo studies show that cRGD-PS-DM1 has a greatly improved toleration as compared with free DM1 and effectively inhibits tumor growth and extends the survival time of B16F10 melanoma-bearing mice. cRGD-PS-DM1 nano-prodrug with reactive drug loading and multifunction provides an advanced nanomedicine for cancer therapy.

• 出版日期2017-10
• 单位苏州大学